These studies are aimed at correlating changes in RNA metabolism that occur during the chemical induction of hepatomas, with the histogenesis of these neoplasms. Hepatomas, both human and experimental, exhibit a number of phenotypic changes which may be due to either genic damage or to errors in the way RNA is transcribed, processed or transported to the cell cytoplasm. Nuclear and cytoplasmic RNA's in livers of rats treated with the aromatic amine, N-2 acetylaminofluorene (AAF), the hepatocarcinogenic alkylating agent, N-N diethylnitrosamine (DEN) and the non-carcinogenic alklylating agent, methyl methane sulfonate (MMS) will be compared with those in normal and damaged but non-neoplastic liver. These comparisons should make it possible to delineate toxic or reactive changes in RNA metabolism from these specific to carcinogenesis. The nuclear and cytoplasmic transcripts from neoplastic and non-neoplastic tissues will be analyzed by several hybridization techniques to assess qualitative and quantitative differences in the composition of the unique sequence RNA's of different abundance classes. The molecular sizes of selected groups of species will be determined. The nature of the sequences of poly A positive and Poly A negative mRNA's and their distribution will be contrasted in preneoplastic and neoplastic liver to elucidate any defects that may exist in the processing and disposition of these messages in the cytoplasm of tumors. The number of copies of a specific messenger, albumin mRNA, present in the cytoplasm, and the distribution of these messenger molecules between free and bound polysomes will be measured in order to determine whether cytoplasmic influences may be responsible for the diminished production and secretion of this protein that often occurs in hepatomas.